Dichotomous Effect of Caffeine, Curcumin, and Naringenin on Genomic DNA of Normal and Diabetic Subjects
30 Mar 2014-Vol. 2014, pp 649261-649261
TL;DR: The objective of this study is to find the dichotomic behavior of caffeine, curcumin, and naringenin on DNA of diabetic and normal subjects in the presence and absence of copper, hydrogen peroxide, and complex of copper-hydrogen peroxide.
Abstract: Nutraceutical compounds show antioxidant and prooxidant properties under stress conditions like cancer, diabetes, and other diseases. The objective of this study is to find the dichotomic behavior of caffeine, curcumin, and naringenin on DNA of diabetic and normal subjects in the presence and absence of copper, hydrogen peroxide, and complex of copper-hydrogen peroxide. Hydrogen peroxide releases hydroxyl free radicals (•OH) on oxidation of Cu (I) to Cu (II) through Fenton-type reaction to cause DNA damage. In the results, agarose gel electrophoretic pattern speculates the prooxidant effect of caffeine and antioxidant effect of curcumin on DNA in the presence of copper and hydrogen peroxide. UV-Vis spectral analysis shows hyperchromism on addition of DNA to caffeine, hypochromism with curcumin, and subtle changes with naringenin. The chosen nutraceuticals act as inducers and quenchers of oxidative free radicals arising from diabetes.
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TL;DR: Dear Editor,Curcumin is a polyphenolic compound with a multitude of beneficial actions for cardiometric health.
58 citations
Cites background from "Dichotomous Effect of Caffeine, Cur..."
...The resulting complex then undergoes an intramolecular electron transfer reaction leading to the formation of semiquinone, superoxide and hydroxyl radicals, respectively (Chattopadhay et al. 2014)....
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...Although polyphenols such as curcumin are powerful antioxidants, it has been shown that these compounds elicit pro-oxidant effects at higher doses (Halliwell 2008; Chattopadhay et al. 2014)....
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TL;DR: The results of the present study may be of relevance in determining the effect of caffeine on the processes induced by ROS in vivo and can be an indication for clinical observations aiming at the assessment of both preventive and therapeutic effects of caffeine in cataract.
Abstract: Introduction One of the major causes of cataract in diabetes is oxidative stress induced by reactive oxygen species (ROS). Nowadays, new substances with antioxidative properties that may prevent cataract development are needed. One such substance is caffeine - an alkaloid with well-documented antioxidative activity. Material and methods The study was conducted on lenses obtained from female rats, divided into 3 groups: control rats; diabetic rats; diabetic rats treated with caffeine at a dose of 20 mg/kg p.o. Type 1 diabetes was induced by streptozotocin (60 mg/kg i.p.). After 4 weeks of caffeine administration, the rats were sacrificed, and the lenses were collected, weighed and homogenized in PBS. The homogenate was used for analysis of protein content, glutathione (GSH) concentration, advanced oxidation protein product (AOPP) concentration, malondialdehyde (MDA) concentration and the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Results The SOD, CAT and GPx activities were found to be higher in the lenses of diabetic rats. There were also increased MDA and AOPP concentrations as well as decreased GSH concentration. The administration of caffeine resulted in decreased activity of SOD, CAT and GPx. The treatment with caffeine also caused an increase of GSH concentration and a decrease of MDA and AOPP concentrations. Conclusions The results of the present study may be of relevance in determining the effect of caffeine on the processes induced by ROS in vivo. Further, they can be an indication for clinical observations aiming at the assessment of both preventive and therapeutic effects of caffeine in cataract.
41 citations
TL;DR: The toxic effect of caffeine appears to be through a mechanism of DNA damage (genotoxic effect) that involves DSB generation since, in all tested conditions, the growth of Δrad52 strain was more severely affected.
Abstract: Caffeine is a compound that can exert physiological–beneficial effects in the organism. Nevertheless, there are controversies about its protective-antioxidant and/or its negative genotoxic effect. To abound on the analysis of the possible genotoxic/antioxidant effect of caffeine, we used as research model the yeast Yarrowia lipolytica parental strain, and mutant strains (∆rad52 and ∆ku80), which are deficient in the DNA repair mechanisms. Caffeine (5 mM) showed a cytostatic effect on all strains, but after 72 h of incubation the parental and ∆ku80 strains were able to recover of this inhibitory effect on growth, whereas ∆rad52 was unable to recover. When cells were pre-incubated with caffeine and H2O2 or incubated with a mixture of both agents, a higher inhibitory effect on growth of mutant strains was observed and this effect was noticeably greater for the Δrad52 strain. The toxic effect of caffeine appears to be through a mechanism of DNA damage (genotoxic effect) that involves DSB generation since, in all tested conditions, the growth of Δrad52 strain (cells deficient in HR DNA repair mechanism) was more severely affected.
3 citations
01 Jan 2018
TL;DR: This chapter deals with the current information available for the cancer chemopreventive activities of curcumin in various in vitro and in vivo cancer models including epidemiological studies and human trials.
Abstract: Cancer has become one of the leading causes of death worldwide. Presently, available chemotherapeutic agents have several limitations including severe side effects. Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa. Curcumin has been used extensively as spice in many Asian countries and in Ayurvedic medicines. It is nontoxic and has shown to possess various medicinal properties including antioxidant, anti-inflammatory, and antibacterial. Recent investigations have shown that curcumin exerts anticancer properties in various cancer cell models and targets variety of biological pathways involved in cell cycle regulation, apoptosis, mutagenesis, angiogenesis, and metastasis. NF-κB, p53, Nrf2, NFAT, MMPs, STATs, and uPA are important molecular targets of curcumin in multiple cancer models. Enzymes involved in redox balance inside the cells including superoxide dismutases, catalase, and glutathione peroxidase are modulated by curcumin. However, bioavailability, water insolubility, short life span, and rapid systemic clearance of curcumin have posed limitations in developing curcumin as an effective chemotherapeutic agent. To address these challenges, curcumin has been used in combinations with many other chemotherapeutic drugs which have shown encouraging results. This chapter deals with the current information available for the cancer chemopreventive activities of curcumin in various in vitro and in vivo cancer models including epidemiological studies and human trials. Also, molecular pathways involved in the manifestation of biological activities of curcumin against various processes of cancer development have been discussed.
3 citations
TL;DR: Curcumin protects the liver against toxin-induced apoptosis, and is suggested to have an anti-apoptotic effect in a dose-dependent manner.
Abstract: Objective: Cadmium (CD), which is used for many industrial purposes, is a toxic agent. CD accumulates in the liver; therefore, exposure to toxic doses of Cd results in hepatic damage. Studies in rats have shown that CD induces apoptosis in hepatocytes. Curcumin is a natural compound isolated from Curcuma longa. It has a powerful anti-inflammatory affect and scavenges reactive oxygen radicals. Additionally, it has been shown to have an anti-apoptotic effect in a dose-dependent manner. The aim of the present study was to evaluate the effects of therapeutic doses of curcumin on Cd-induced hepatic apoptosis as well as hepatic biochemical and inflammatory changes in Sprague-Dawley rats. Methods: In this study, 24 female Sprague-Dawley rats (6 months old) were randomly assigned to four main groups (n=6): control, CD, CD +curcumin, and curcumin. At the end of the experiment, after collecting blood samples from the heart, the rats were sacrificed and their livers were removed for histopathological and biochemical examinations. The number of apoptotic cells, total anti-oxidant status, total oxidant status, and thiol and MPO levels were measured in liver tissue; interleukin-6 and procalcitonin levels were measured in sera. Results: Chronic CD administration induced apoptosis. The number of apoptotic cells was significantly increased in the Cd group (almost 2 fold) compared to that in the control group. However, in the CD+curcumin group, the number of apoptotic cells was significantly decreased (almost 2 fold) compared to that in the Cd group. However, there were no statistically significant differences. Conclusion: We suggest that curcumin protects the liver against toxin-induced apoptosis.
2 citations
Cites background from "Dichotomous Effect of Caffeine, Cur..."
...In different studies, it has been reported that curcumin is a dose-dependent prooxidant (38, 39)....
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References
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TL;DR: This review critically addresses the extent to which the in vitro significance of oxidative DNA damage has relevance for the pathogenesis of disease, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage.
Abstract: Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.
2,910 citations
"Dichotomous Effect of Caffeine, Cur..." refers background in this paper
...The oxidative stress caused by diabetes is accompanied by production of reactive oxygen species (ROS) (hydroxyls, superoxides, peroxides), which can generate potential damage to mammalian deoxyribonucleic acid (DNA) [1]....
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TL;DR: Experimental approaches to the optimization of antioxidant nutrient intake are proposed, and interest is also growing in the role of plant phenolics, especially flavonoids.
Abstract: Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H2O2-removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so diet-derived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed.
1,796 citations
"Dichotomous Effect of Caffeine, Cur..." refers background in this paper
...The extent of hydroxyl radicals causing damage to DNA of diabetic patients is higher compared to healthy humans [5]....
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TL;DR: In the cross-sectional studies conducted in northern Europe, southern Europe, and Japan, higher coffee consumption was consistently associated with a lower prevalence of newly detected hyperglycemia, particularly postprandial hyperglyCEmia.
Abstract: ContextEmerging epidemiological evidence suggests that higher coffee consumption
may reduce the risk of type 2 diabetes.ObjectiveTo examine the association between habitual coffee consumption and risk
of type 2 diabetes and related outcomes.Data Sources and Study SelectionWe searched MEDLINE through January 2005 and examined the reference
lists of the retrieved articles. Because this review focuses on studies of
habitual coffee consumption and risk of type 2 diabetes, we excluded studies
of type 1 diabetes, animal studies, and studies of short-term exposure to
coffee or caffeine, leaving 15 epidemiological studies (cohort or cross-sectional).Data ExtractionInformation on study design, participant characteristics, measurement
of coffee consumption and outcomes, adjustment for potential confounders,
and estimates of associations was abstracted independently by 2 investigators.Data SynthesisWe identified 9 cohort studies of coffee consumption and risk of type
2 diabetes, including 193 473 participants and 8394 incident cases of
type 2 diabetes, and calculated summary relative risks (RRs) using a random-effects
model. The RR of type 2 diabetes was 0.65 (95% confidence interval [CI], 0.54-0.78)
for the highest (≥6 or ≥7 cups per day) and 0.72 (95% CI, 0.62-0.83)
for the second highest (4-6 cups per day) category of coffee consumption compared
with the lowest consumption category (0 or ≤2 cups per day). These associations
did not differ substantially by sex, obesity, or region (United States and
Europe). In the cross-sectional studies conducted in northern Europe, southern
Europe, and Japan, higher coffee consumption was consistently associated with
a lower prevalence of newly detected hyperglycemia, particularly postprandial
hyperglycemia.ConclusionsThis systematic review supports the hypothesis that habitual coffee
consumption is associated with a substantially lower risk of type 2 diabetes.
Longer-term intervention studies of coffee consumption and glucose metabolism
are warranted to examine the mechanisms underlying the relationship between
coffee consumption and type 2 diabetes.
632 citations
TL;DR: Both the estimated rates of ADP phosphorylation by glycolysis and mitochondria and the estimated rate of ATP hydrolysis by ongoing metabolism were utilized to model the approximate decline in intracellular ATP expected at 15-min exposure to various H2O2 concentrations.
620 citations
"Dichotomous Effect of Caffeine, Cur..." refers background in this paper
...Hydrogen peroxide has poor radical activity, but at higher concentration (>50μM) through the formation of hydroxyl radical, it can cause DNA strand breakage and base modification [4]....
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TL;DR: In this article, the benefits of antioxidant therapies in the prevention/treatment of diabetic cardiovascular complications are discussed, where the authors show that appropriate glycemic control, in which both hypoglycemic and hyperglycemic episodes are reduced, in association to the treatment of dyslipidemia, hypertension, kidney dysfunction and obesity, conditions which are also associated to reactive oxygen species (ROS) overproduction, can counteract oxidative stress and, therefore, both microvascular and macrovascular complications of diabetes mellitus.
Abstract: Diabetes mellitus is associated to an increased risk of cardiovascular diseases. Hyperglycemia is an important factor in cardiovascular damage, working through different mechanisms such as activation of protein kinase C, polyol and hexosamine pathways, advanced glycation end products production. All of these pathways, in association to hyperglycemia-induced mitochondrial dysfunction and endoplasmic reticulum stress, promote reactive oxygen species (ROS) accumulation that, in turn, promote cellular damage and contribute to the diabetic complications development and progression. ROS can directly damage lipids, proteins or DNA and modulate intracellular signaling pathways, such as mitogen activated protein kinases and redox sensitive transcription factors causing changes in protein expression and, therefore, irreversible oxidative modifications. Hyperglycemia-induced oxidative stress induces endothelial dysfunction that plays a central role in the pathogenesis of micro- and macro-vascular diseases. It may also increase pro-inflammatory and pro-coagulant factors expression, induce apoptosis and impair nitric oxide release. Oxidative stress induces several phenotypic alterations also in vascular smooth-muscle cell (VSMC). ROS is one of the factors that can promote both VSMC proliferation/migration in atherosclerotic lesions and VSMC apoptosis, which is potentially involved in atherosclerotic plaque instability and rupture. Currently, there are contrasting clinical evidences on the benefits of antioxidant therapies in the prevention/treatment of diabetic cardiovascular complications. Appropriate glycemic control, in which both hypoglycemic and hyperglycemic episodes are reduced, in association to the treatment of dyslipidemia, hypertension, kidney dysfunction and obesity, conditions which are also associated to ROS overproduction, can counteract oxidative stress and, therefore, both microvascular and macrovascular complications of diabetes mellitus.
585 citations
"Dichotomous Effect of Caffeine, Cur..." refers background in this paper
...Overproduction of ROS in the presence of limited availability of antioxidants augments the oxidative stress induced damage on proteins, lipids, andDNA, impairing their function [28]....
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...The oxidative stress caused by diabetes is accompanied by production of reactive oxygen species (ROS) (hydroxyls, superoxides, peroxides), which can generate potential damage to mammalian deoxyribonucleic acid (DNA) [1]....
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...Oxidative stress arises due to an imbalance between production and consumption of ROS and presence of metals exacerbates the generation of free radicals....
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...ROS is involved in blocking the pathway between insulin-receptor substrate (IRS-1) and phosphatidylinositol-4,5-bisphosphate 3-kinase to result in high insulin resistance [6]....
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...Hyperglycemia induced oxidative stress promotes production of reactive oxygen species (ROS) [27]....
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